Join our email list!

Get daily updates delivered to your inbox
Thank you for subscribing

There Is No Magic Pill for MS Fatigue

There Is No Magic Pill for MS Fatigue

I’ve been tired all day, which is nothing new, as fatigue and multiple sclerosis go hand in hand. It’s been one of my primary symptoms since I was diagnosed in 1980.

To counter it, I’ve taken Provigil (modafinil) for many years. Initially, taking 100 mg in the morning helped me make it through the day. But as time went on, Provigil’s effectiveness waned.

The year before I retired eight years ago, I’d occasionally start to doze off in my office, or worse, while driving home from work. Recently, I began to wonder if Provigil was working for me at all. Today, while visiting our young grandkids, I was dragging; my eyes were open, but I had no energy, even though I’d taken my medication less than two hours earlier.

Could the benefits be in my head?

Interestingly, a day earlier, I read a study in The Lancet Neurology that looked at three medications commonly prescribed for MS fatigue: modafinil, methylphenidate, and amantadine. (In the U.S., methylphenidate is marketed as Ritalin, among others.) The results surprised me.

In the study, 136 MS patients who had their fatigue measured by the Modified Fatigue Impact Scale (MFIS) were rotated through the trio of fatigue medications plus a placebo, spending six weeks on each. Their fatigue levels were measured based on the MFIS after each medication.

Guess what? The medications appear to have done no better than the placebo. Take a look at the estimated mean values of MFIS total scores at baseline and the maximal tolerated dose for each:

  • Score at baseline: 51.3
  • Score after placebo: 40.6
  • Score after amantadine: 41.3
  • Score after modafinil: 39.0
  • Score after methylphenidate: 38.6

Also, while the medications didn’t prove to be better than the placebo in improving MS fatigue, they did result in more frequent adverse events. So, considering the risks and the benefits, the researchers concluded that “the results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.”

Does this surprise you?

People with MS have been using these medications for years in an effort to tame the fatigue monster, so it’s no wonder I was surprised by these results. Maybe I shouldn’t have been. The folks at the National MS Society (NMSS) remind us that no medications are approved specifically to treat MS fatigue. Everything that people with MS use is prescribed off-label.

Clinical trials of meds for MS fatigue have produced mixed results. As the Cleveland Clinic’s website reports, two studies have looked at modafinil’s effects on MS fatigue. One “showed a significant effect on fatigue, but the other did not.” Interestingly, the clinic also noted that a recent study found that taking two regular aspirins twice a day significantly reduced MS fatigue.

Lessening MS fatigue without medications

The NMSS and the Cleveland Clinic both suggest fatigue-reducers such as exercise, physical therapy, and relaxation therapy. Multiple Sclerosis News Today patient columnist Jessie Ace shared some other ideas a few months ago. But I think most of us have tried nonmedicinal strategies and only turned to medications when those therapies didn’t help enough.

I tried going without my 100 mg dose of Provigil in the morning yesterday, and I didn’t feel much more tired in the late afternoon than I usually do. I think I’ll try this unscientific experiment again, but over two or three days, to see what happens.

Has there been fatigue-relieving magic in the pill I’ve been taking all these years, or has it all been in my head?

What has your experience been? Please share in the comments below. You’re also invited to visit my personal blog at


Note: Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Multiple Sclerosis News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to multiple sclerosis.

Diagnosed with MS at age 32 in 1980, Ed has written the “MS Wire” column for Multiple Sclerosis News Today since August 2016. He presents timely information on MS, blended with personal experiences. Before retiring from full-time work in 2012, Tobias spent more than four decades in broadcast and on-line newsrooms as a manager, reporter, and radio news anchor. He’s won several national broadcast awards. As an MS patient communicator, Ed consults with healthcare and social media companies. He’s the author of “We’re Not Drunk, We Have MS: A tool kit for people living with multiple sclerosis.” Ed and his wife split time between the Washington, D.C. suburbs and Florida’s Gulf Coast.
Diagnosed with MS at age 32 in 1980, Ed has written the “MS Wire” column for Multiple Sclerosis News Today since August 2016. He presents timely information on MS, blended with personal experiences. Before retiring from full-time work in 2012, Tobias spent more than four decades in broadcast and on-line newsrooms as a manager, reporter, and radio news anchor. He’s won several national broadcast awards. As an MS patient communicator, Ed consults with healthcare and social media companies. He’s the author of “We’re Not Drunk, We Have MS: A tool kit for people living with multiple sclerosis.” Ed and his wife split time between the Washington, D.C. suburbs and Florida’s Gulf Coast.

How useful was this post?

Click on a star to rate it!

Average rating 4.7 / 5. Vote count: 37

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?


  1. Jackie Topp says:

    An interesting article. I have just been prescribed methylphenidate for concentration rather than fatigue. My fatigue is a major affect despite trying modafinil. I’ve resigned myself to being this way and not trying to fight it.
    I am finding my concentration is better focused,, so maybe will find fatigue will improve as a result- even if it is slight. 🤔

  2. Cynthia says:

    I was diagnosed in1987 , but had my first symptoms in 1969. Fatigue was one of the first. I was told , in 1987 , to try aspirin for fatigue. It worked for me , and continues to be my choice , when feeling overwhelmed.Perhaps it is “all in my head ” that it works ….but , if I feel better , and am better able to cope ….I will continue to use it . My dose is low ( one 325 mg. pill , and not every day …. only when overwhelmed with fatigue.
    Also , I find that I have far less disabling fatigue since I began medical cannabis oil 2 years ago.
    These appear to work for me.

    • Ed Tobias says:

      Hi Cynthia,

      Thanks for sharing all of that. I’d much rather take aspirin so maybe I’ll give that a try.

      Would you be willing to share the dose of medical cannabis oil you use and its THC/CBD mix? That would be useful.



      • Cynthia says:

        Hi ,Ed
        I just want to add , I drink a cup of coffee with my aspirin. They say that caffeine boosts the effect of aspirin.
        I take 1 ml. of cbd oil during the day <1mg. THC and 20mg. CBD
        At bedtime , I take oil containing equal parts cbd and thc
        10mg. of each I

  3. Steve Bunting says:

    Hi, I have been on Amantadine for the last 14 years. I have taken Amantadine holidays at odd times during the period but I have thought I didn’t think it was doing anything for me. The doctors just tell me to take another dose at lunch time which i have not been convinced by either. Your findings are useful and will make me consider stopping taking them.

    • Ed Tobias says:

      Thanks for your comments, Steve. I’m glad my info was useful but please don’t make any changes based on what I wrote without discussing it with your own physician.


  4. My experience with MS patients since 2010 shows that the use of cord blood stem cell transfusions significantly reduces the rate of fatigue. It is my hope that regulatory authorities will consider incorporating cell therapy into the standard of care for patients with multiple sclerosis.

    • Ed Tobias says:

      Thanks for sharing that, Vadim.

      Stem cell replacement therapy, of course, is much more available in Russia than it is in the US. (I assume that’s where you are). But I also hope that authorities here will make it more available before too long.


  5. Jim-Bob says:

    Armodafinil has improved my life with strongly noticable effect. I quarter a 250 mg tablet, and take one quarter most days, then 2 quarters on days I want a boost. Or as a routine every 3rd day. If I take 2 quarters every day, it loses its effectiveness after a bit.

    I have also noticed that when Armodafinil isnt effective I may be exhausted, and taking GABA and a very small dose of melatonin (0.5 mg) about four hours before bed acts as a reset, and then the Armodafinil be effective again. If you havent tried this enantiopure version of Modafinil you should, it is much much more effective for me.

  6. Jim-Bob says:

    Also, sometimes I experience leg weakness that is thought to be neurological rather than musculoskeletal. This seems to correlate with the times when I can no longer be on my feet after 6 PM due to sheer exhaustion. I have found that taking Phentermine helps this problem greatly. I dont like stimulants, and this is definitely a stimulant effect for me, so I use it sparingly. But I know when the 6 PM exhaustion hits, I stop taking Armodafinil for a couple days and then start taking Phentermine in the morning and it helps quite a bit to extend my day for a couple hours, which is critical if I am working daylight hours. Obviously you need to consult with your doctor about how to transition between these drugs to avoid overlap.

  7. Janis Sholtis says:

    I have been taking Medterra CBD oil for some time for arthritis pain. I have recently tried a new product of theirs called Good Morning. It has liposomal CBD, caffeine, B6, B12, maca and turmeric in a capsule, designed to give you a boost in the morning. I have been taking it later in the day when I feel like I can’t go another minute but really can’t stop to rest. It gets me over the hump to finish my day. That’s my miracle pill.

  8. Janette Murphy says:

    Hi, I have had MS for just over 12 months and the fatigue is challenging.
    I take Modafinil once a week to improve my alertness when interpreting (sign language) the Mass each Sunday for the Deaf Community. It certainly helps with my alertness and ability to process the information I’m receiving.
    I did take Modafinil over a few days when preparing for an Oral Comprehensive Exam, and I found it had less effect rather than an improved effect. Which I found interesting. Based on my experience I would not take it daily, and find it works well for me when I take it each Sunday as I’m more able to process the information without getting stressed.
    I found with taking it more often I was experiencing the anxiety aspects associated with it.
    Once a week doesn’t relieve the fatigue issue, but it does enable me to function effectively in the interpreting situation.

    • Ed Tobias says:

      Thanks for sharing that info, Janette.

      It may be that occasional use is more effective than daily. Over time the body may become more accustomed to the medication.

      We all need to figure out what’s best for ourselves, even after 40 years with MS.


  9. Terry says:


    I was diagnosed with MS at 32 in 1988. Started taking 200mg of Provigil after reading about our fighter pilots on long sorties using it in the ME. After bad headaches for a week, it was just what was needed to get me going again. In 2013, it began to lose its effectiveness so Doc upped me another 200mg, one in the morning and one in the afternoon. Back on track once again.

    Then insurance issues forced the generic modafinel. It’s never been the same. It’s not the same. Even though they are supposed to be the same, they are not.

    I am down to one 200mg of modafinel a day now due to weird blood results. After this script is finished, don’t plan to refill as it does nothing for me. I’ll just keep guzzling coffee!

    • Ed Tobias says:

      Hi Terry,

      I never thought about an efficacy difference between brand-name and generic. Good point.

      I can’t wait to return to exercising. Meanwhile, I’ll join you in a cuppa. I love my morning Italian or French blend.


  10. Lenore White says:

    I was diagnosed with MS 7 years ago after an acute episode of Transverse Myelitis several years before. Fatigue initially was an issue for me. As nurse, I am aware that if a 100% well person decreased their activity markedly they would also suffer with muscle weakness and fatigue. So I decided to keep the well parts of my body and healthy and active as I could letting my weak part go along for a free ride as much as possible. I started swimming with 2 good arms and 1 good leg. At first I could only manage a few lengths but after a few months I could swim 2 kilometers. Now, I go to a gym twice a week and run 2 k on a cross trainer, ride a bike for 45 minutes and lift weights for half an hour. I am 70 years of age and feel and look great.Increasing exercise is also beneficial for mood and a positive outlook. I still have to pace myself and know that I will need to plan for a few lazy days after being busy.And that is OK too!!

    • Ed Tobias says:

      Hi Lenore,

      I like your attitude!

      I, too, like swimming and exercise. I was up to 20 minutes on a recumbent bike and spent half an hour on upper body weight machines every other day. Then, COVID hit. It seems your government in New Zealand handled this pandemic extremely well. On the other hand, our cases keep climbing and using the gym or pool are on hold for me until I’ve been jabbed with a vaccine.


  11. Christian fernandes says:

    Hi Ed Tobias,
    I was wondering if there is no possibility of focusing much more and regularly on the use of natural substances (nutrients like vitamin B12, vitaminD, unsaturated fatty acids; nutraceuticals like coenzyme Q10, N-acetylglucosamine; herbals) in regard to the treatment of MS. My girlfriend has MS and she realy is avoiding the use of the regular MS~drugs because of all the know side effects.
    Thank you in advance.

    • Ed Tobias says:

      Hi Christian,

      Thanks for your comments.

      I’ve occasionally written about natural treatments and diets. However, most of what I write is based upon my personal experiences and most of my experiences, over 40 years living with MS, have involved medications and exercise.

      There are many who believe that natural treatments are superior to drugs, but I think you’ll find that most research shows that medications provide the best chance of slowing or stopping MS progression.


  12. Gale Langseth Vester says:

    I usually take one Modafinil in the morning. One pill lasts me through the day, but another half can be added in the afternoon, if needed.

    Oddly, I felt my energy level lowering just before reading this article at 2:30 in the afternoon. Taking half a Modafinil, I then started reading. See, it isn’t some kind of suggestible med need! 8^D

    • Ed Tobias says:

      Hi Gale,

      It’s around 3:00pm as I’m writing this and it’s the start of my usual 3pm – 7pm energy dip. But, this morning I didn’t take my usual 100mg modafinil. And, I’m not tired right now.

      You just never know with MS :-).


  13. Sue says:

    Hi Ed, I was dx’d in 2001 with fatigue as one of my biggest issues. I am currently on 2x200mg Modafinil in AM and I feel it barely touches it. I was just assigned a new Neuro out of UofC and he was shocked at how much I am already taking. Based on feedback in this thread as well his recommendation I will try breaking them up during the day. I have previously gone off of the Modafinil for up to a year and really did not notice much improvement when I went back on. I call it my “melt” factor when fatigue kicks in, in earnest; it seems to be happening earlier in the day as the years progress. TY for your sharing your findings! Stay safe, stay well!

  14. Sharon Gray says:

    Hello. I was diagnosed at 29 years old and I am now hitting 60. I have used Provigil and generic brand since I was diagnosed. It helps me so much with the fatigue much also then helps with my mood/depression. I have tried not taking for a short time but and can tell the biggest difference. Of course everyone’s MS is different so, what works for one person many not work for another.

Leave a Comment

Your email address will not be published. Required fields are marked *